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Biomedical subjects

M M Lerch

Publications and source records attributed to M M Lerch.

At least 19 recordsLinked to original sources
PubMed2003

Papillary mesothelioma of the peritoneum in the absence of asbestos exposure.

BACKGROUND: Malignant mesothelioma of the peritoneum is a very rare neoplasm, commonly associated with asbestos exposure and often rapidly fatal. Well Differentiated Papillary Mesothelioma of the Peritoneum (WDPMP) is regarded as a less aggressive variety of the tumor. Progressive ascites is often the only clinical manifestation of the disease and differentiation of WDPMP from benign mesothelial hyperplasia or adenocarcinoma is difficult. PATIENTS AND METHODS: Here we report the case of a 45-year-old patient who presented with ascites but without evidence of portal hypertension, liver disease or abdominal malignancy. On diagnostic laparoscopy small tumor nodules were found to cover the parietal peritoneum and the greater omentum and histopathologically corresponded to papillary mesothelial hyperplasia with minimal nuclear atypia. Histochemically biopsies were positive for Calretinin, Cytokeratins and Epithelial Membrane Antigen (EMA). Based on these findings the diagnosis of WDPMP was made and the patient was closely followed without primary cytostatic therapy. CONCLUSIONS: Progressive ascites was the only clinical symptom in this patient, while liver disease, portal hypertension and gastrointestinal malignancies were ruled out by clinical, laboratory and imaging techniques. Laparoscopic biopsy revealed WDPMP to be the underlying disease. Immunocytochemistry is required to establish the diagnosis of this rare malignant disorder which is even more uncommon in the absence of a history of asbestos exposure. Due to the indolent course of WDPMP therapy should only be initiated when signs of rapid tumor progression become apparent.

Asbestosis↗
PubMed2002

The N34S mutation of SPINK1 (PSTI) is associated with a familial pattern of idiopathic chronic pancreatitis but does not cause the disease.

BACKGROUND: Mutations in the PRSS1 gene explain most occurrences of hereditary pancreatitis (HP) but many HP families have no PRSS1 mutation. Recently, an association between the mutation N34S in the pancreatic secretory trypsin inhibitor (SPINK1 or PSTI) gene and idiopathic chronic pancreatitis (ICP) was reported. It is unclear whether the N34S mutation is a cause of pancreatitis per se, whether it modifies the disease, or whether it is a marker of the disease. PATIENTS AND METHODS: A total of 327 individuals from 217 families affected by pancreatitis were tested: 152 from families with HP, 108 from families with ICP, and 67 with alcohol related CP (ACP). Seven patients with ICP had a family history of pancreatitis but no evidence of autosomal dominant disease (f-ICP) compared with 87 patients with true ICP (t-ICP). Two hundred controls were also tested for the N34S mutation. The findings were related to clinical outcome. RESULTS: The N34S mutation was carried by five controls (2.5%; allele frequency 1.25%), 11/87 (13%) t-ICP patients (p=0.0013 v controls), and 6/7 (86%) affected (p<0.0001 v controls) and 1/9 (11%) unaffected f-ICP cases. N34S was found in 4/108 affected HP patients (p=0.724 v controls), in 3/27 (11%) with wild-type and in 1/81 (1%) with mutant PRSS1, and 4/67 ACP patients (all p>0.05 v controls). The presence of the N34S mutation was not associated with early disease onset or disease severity. CONCLUSIONS: The prevalence of the N34S mutation was increased in patients with ICP and was greatest in f-ICP cases. Segregation of the N34S mutation in families with pancreatitis is unexplained and points to a complex association between N34S and another putative pancreatitis related gene.

Adult↗
PubMed2002

Lymphocyte apoptosis after exhaustive and moderate exercise.

Apoptosis or programmed cell death is a process of fundamental importance for regulation of the immune response. Several reasons suggest that apoptosis is involved in exercise-induced alterations of the immune system such as postexercise lymphocytopenia. Healthy volunteers performed two treadmill exercise tests; the first was performed at 80% maximal oxygen uptake until exhaustion (exhaustive exercise) and the second 2 wk later at 60% maximal oxygen uptake with the identical running time (moderate exercise). Blood samples were taken before, immediately after, and 1 h after the test. Lymphocytes were analyzed for apoptotic and necrotic cells by using FITC-labeled annexin V-antibodies and nuclear propidium iodide uptake, respectively. In addition, apoptotic/necrotic cells were measured after a 24-h incubation of lymphocytes in the presence of camptothecin or phytohemagglutinin. Finally, plasma membrane expression of CD95-receptor and CD95-receptor ligand was investigated. Immediately after the exhaustive exercise, the percentage of apoptotic cells increased significantly, whereas it remained unchanged after the moderate exercise. Similar results were obtained after 24-h incubation of lymphocytes in medium alone or in the presence of camptothecin, but not with phytohemagglutinin. We found an upregulation of CD95-receptor expression after both exercise tests. However, only after exhaustive exercise a characteristic shift in CD95 expression profile toward cells with a high receptor density was observed. Expression of the CD95-receptor ligand remained unchanged after both exhaustive and moderate exercise. These results suggest that apoptosis may contribute to the regulation of the immune response after exhaustive exercise. Whether this mechanism can be regarded either as beneficial, i.e., deletion of autoreactive cells, or harmful, i.e., suppression of the immune response, awaits further investigations.

Adult↗
PubMed2001

Clinical characterization of patients with hereditary pancreatitis and mutations in the cationic trypsinogen gene.

PURPOSE: We determined the clinical manifestations of hereditary pancreatitis in nearly 30 families. PATIENTS AND METHODS: The two trypsinogen mutations N29I and R122H were identified in a group of 550 patients with chronic pancreatitis of unclear origin. The following criteria were used to characterize the severity of chronic pancreatitis (one point each): calcifications, cysts, dilation of the pancreatic duct, diabetes, hospital treatment, and operation. Stages were defined as stage 0 (no points), stage 1 (one to two points), stage 2 (three to four points), and stage 3 (more than four points). Smoking and drinking habits were also recorded. RESULTS: Six families with the N29I mutation (25 subjects with the mutation) and 21 families with the R122H mutation (76 subjects with the mutation) were identified. The median ages for the onset of disease were 11 years in N29I and 10 years in R122H patients. The severity of chronic pancreatitis and symptoms were similar for both mutations. About 26% (n = 26) of the 101 subjects carrying a mutation were asymptomatic, and 42% (n = 42) had mild disease (stage 1). Twenty-nine percent (n = 29) had moderate disease (stage 2), and only 4% (n = 4) had severe disease (stage 3). CONCLUSIONS: Symptoms of patients with the N29I or R122H trypsinogen mutation were generally similar. The majority of subjects with trypsinogen mutations had mild disease or was asymptomatic.

Adolescent↗
PubMed2001

[Fulminant liver failure after administration of the herbal antidepressant Kava-Kava].

HISTORY AND CLINICAL FINDINGS: A 60 year-old woman was admitted to hospital because of jaundice, fatigue, weight loss over several months and icteric skin. Because of progressive liver failure, concomitant renal failure and progressive encephalopathy she was transferred to an intensive care unit. INVESTIGATIONS: Biochemical tests revealed acute liver failure with high levels of total and conjugated bilirubin (30 mg/dl) as well as aspartate aminotransferase (921 IU/l) and alanine aminotransferase (1350 IU/l) concentrations. Prothrombin time was less than 10 %. Serological tests could rule out viral hepatitis, metabolic or autoimmune causes of liver failure. On abdominal computed tomography and ultrasonography no pathological changes were detected. Above all portal vein thrombosis, ascites, focal lesions of the liver and extrahepatic cholestasis could be excluded. Liver histology showed extensive hepatocellular necrosis with intrahepatic cholestasis. TREATMENT AND CLINICAL COURSE: The patient's physical condition deteriorated. She had to be intubated because of respiratory insufficiency and encephalopathy stage IV. Because of progressive liver failure under conservative treatment the patient received an orthotopic liver transplant 11 days after admission. CONCLUSIONS: The exclusion of other causes and the histological diagnosis made Kava-Kava as the cause of acute liver failure most likely. This is the 18th case of Kava-Kava induced liver failure reported to the European regulatory authorities.

Alanine Transaminase↗
PubMed2001

Effect of hyperthermia on premature intracellular trypsinogen activation in the exocrine pancreas.

Hyperthermia, raising the body temperature from normal to above 40 degrees C, has been shown to prevent pancreatitis in an experimental animal model of the disease, but the underlying cellular mechanisms of this protection remain unknown. We induced controlled hyperthermia in either laboratory rats and isolated pancreatic acini or, alternatively, raised the temperature of pancreatic homogenates in vitro from 37 to 41 degrees C. In vitro controlled hyperthermia of up to 41 degrees C increased the autoactivation-induced and enterokinase-induced trypsinogen activation as well as free trypsin activity. Conversely, in whole animal studies and in living acinar cells hyperthermia reduced or abolished premature intracellular trypsinogen activation in a time- and temperature-dependent manner and this protective effect was independent of either de novo protein synthesis, interference with acinar cell signal transduction, or confirmational changes in pancreatic trypsinogen. We conclude that hyperthermia, in a manner that is independent of the synthesis of pancreatic chaperone or heat shock proteins, can directly abolish the earliest initiating event involved in the onset of pancreatitis, namely the premature and intracellular activation of digestive zymogens.

Animals↗
PubMed2001

Autocrine stimulation of human pancreatic duct-like development by soluble isoforms of epimorphin in vitro.

Epimorphin was recently described as a mesenchymal factor modulating morphogenesis of murine mammary ducts, skin, liver, and lung in vitro. In this study epimorphin was analyzed in a human, pancreatic adenocarcinoma cell line (A818-6) which develops single layer epithelial hollow spheres resembling normal pancreatic ductal structures in vitro. Soluble 34- and 31-kD isoforms of epimorphin were found in the culture supernatant of A818-6 cells. In lysates of A818-6 cells we detected the 34-and 31-kD isoforms and the dimers, and in lysates of fibroblasts the 150-kD tetramers of epimorphin additionally. A neutralizing monoclonal antibody against epimorphin (MC-1) efficiently blocked the development of hollow sphere structures from A818-6 cells. Coculture of A818-6 cells with fibroblasts stimulated the development of hollow sphere structures in general and increased differentiation in 5-6-d-old hollow spheres. A818-6 hollow sphere development in the presence of fibroblasts was also blocked by MC-1. In this novel system for human duct-like differentiation of pancreatic epithelial cells, we provide evidence for an autocrine and paracrine function of epimorphin as a major mediator for morphogenesis.

Adenocarcinoma↗
PubMed2001

[MARS (Molecular Adsorbent Recycling System) as a novel hepatic detoxification procedure until orthotopic liver transplantation].

MARS (Molecular Adsorbent Recycling System) as a novel hepatic detoxification procedure until orthotopic liver transplantation. We report the case of a 30-year-old man who was admitted because of acute liver failure due to longstanding ethanol abuse. On conservative treatment liver function progressively deteriorated and the patient was listed for orthotopic liver transplantation. Because of a rapidly progressive and clinically severe hepatic encephalopathy together with increasing bilirubin levels (maximum 39 mg/dl) we began intermittent extracorporeal detoxification with the Molecular Adsorbent Recycling System (MARS). Under MARS therapy serum bilirubin decreased significantly (to 20 mg/dl after three cycles) and encephalopathy improved rapidly until the patient was completely oriented. No effect of MARS on liver function could be demonstrated. MARS treatment was successfully continued until a cadaver liver became available after 48 days and the patient was transplanted in good clinical and neurological condition and without complications. MARS represents a novel detoxification technique which, in patients with acute liver failure, can successfully replace hepatic detoxification until orthotopic liver transplantation can be performed.

Adult↗
PubMed2001

Calcium-magnesium interactions in pancreatic acinar cells.

Although the role of calcium (Ca2+) in the signal transduction and pathobiology of the exocrine pancreas is firmly established, the role of magnesium (Mg2+) remains unclear. We have characterized the intracellular distribution of Mg2+ in response to hormone stimulation in isolated mouse pancreatic acinar cells and studied the role of Mg2+ in modulating Ca2+ signaling using microspectrofluorometry and digital imaging of Ca2+- or Mg2+-sensitive fluorescent dyes as well as Mg2+-sensitive intracellular microelectrodes. Our results indicate that an increase in intracellular Mg2+ concentrations reduced the cholecystokinin (CCK) -induced Ca2+ oscillations by inhibiting the capacitive Ca2+ influx. An intracellular Ca2+ mobilization, on the other hand, was paralleled by a decrease in [Mg2+]i, which was reversible upon hormone withdrawal independent of the electrochemical gradients for Mg2+, Ca2+, Na+, and K+, and not caused by Mg2+ efflux from acinar cells. In an attempt to characterize possible Mg2+ stores that would explain the reversible, hormone-induced intracellular Mg2+ movements, we ruled out mitochondria or ATP as potential Mg2+ buffers and found that the CCK-induced [Mg2+]i decrease was initiated at the basolateral part of the acinar cells, where most of the endoplasmic reticulum (ER) is located, and progressed from there toward the apical pole of the acinar cells in an antiparallel fashion to Ca2+ waves. These experiments represent the first characterization of intracellular Mg2+ movements in the exocrine pancreas, provide evidence for possible Mg2+ stores in the ER, and indicate that the spatial and temporal distribution of intracellular Mg concentrations profoundly affects acinar cell Ca2+ signaling.

Animals↗
PubMed2001

Acute and chronic pancreatitis in patients with inborn errors of metabolism.

Acute and chronic recurrent pancreatitis have been reported in patients with a variety of inborn errors of metabolism. Among these are hyperlipidaemias, various disorders of branched-chain amino acid degradation, homocystinuria, haemolytic disorders, acute intermittent porphyria and several amino acid transporter defects. Some of these disease entities are exceedingly rare. In most of these disorders, pancreatitis is not very common and, with the exception of lipoprotein lipase and apolipoprotein C-II deficiency, is neither the leading nor the clinically most distressing manifestation of the underlying metabolic defect. The majority of these syndromes are, however, inherited, and often entire kindreds are carriers of well-defined germline mutations that can, to varying degrees, be associated with pancreatitis. We have reviewed the clinical, biochemical and genetic characteristics of those inborn errors of metabolism because interesting information can be gained from the in regard to the pathophysiology of pancreatitis and because they need to be distinguished from other hereditary causes of the disease.

Acute Disease↗
PubMed2001

[Course of illness in acute pancreatitis].

The incidence of acute pancreatitis per year is estimated to be between 10 and 46 per 100,000 population. The mortality rate of acute edematous pancreatitis is below 1%, whereas patients suffering from hemorrhagic-necrotizing pancreatitis die in 10-24% of cases. In 80% acute pancreatitis is caused by either gallstone disease or excessive alcohol consumption. As of today no specific therapy has been developed for the treatment for acute pancreatitis. Acute pancreatitis is characterized by specific clinical and morphological alterations that occur in a time dependent manner. Frequently occurring complications are parenchymal necrosis (15-25%), multiorgan failure (10-26%), pancreatic pseudocysts (5-15%), recurrence of pancreatitis (21%) endocrine (6.5%) and exocrine (13-27%) insufficiency and a transition to chronic pancreatitis (10-25%).

Causality↗
PubMed2001

[Cooperation between clinicians and pathologists].

To the disadvantage of physician in training and quality control the number of post mortem examinations has declined in many Western countries including Germany. The frequency at which surgical or biopsy specimens are investigated by pathologist, on the other hand, appears to increase and clinicians have become increasingly more reliant on a pathologists assessment in terms of diagnosis and treatment strategy. There are some areas where communication between clinician and pathologist could be improved. The first regards the classification of malignancies which should, wherever possible, follow international guidelines such the WHO's. From a clinicians perspective assessment of tumour staging and grading should be based on the patient's prognosis rather than morphological criteria alone. In the case of rare tumours, for which the clinician can be assumed to be ignorant, reference to the literature is helpful. If the surgical or biopsy specimen reveals a malignancy that cannot be classified suggestions for a differential diagnosis can be still helpful. Frequently, at least in my field of speciality, the only tissue accessible is a hepatic or lymphatic metastasis. Determination of the tumour of origin is often essential in deciding on treatment options and every effort including immonocytochemical methods should be made to help to determine the tumour's original site. It spares enormous cost and makes many unpleasant interventional procedures redundant. Further areas where clinicians increasingly need help from pathologists are the diagnosis of inflammatory and infectious diseases and in the usage of molecular genetic methods.

Autopsy↗